Who should be receiving therapeutic hypothermia?

Thanks to the popularity of medical television shows, most people have witnessed hundreds of fictional cardiac arrests in their lifetime. In most of these scenes, the patient loses consciousness, and the medical team rushes to the bedside:

“He’s in v-fib.”

“Get me the paddles.”

The team performs urgent chest compressions for a few seconds. Then they place the metal paddles on the victim’s chest:

“Clear!” Kathump.

The patient’s heart is back to normal again, tragedy avoided.

On television, the outcomes of in-hospital resuscitations are commonly miraculous. According to a NEJMstudy from 1996, over 75% of “patients” who received CPR on popular television shows were brought back to life by the treatment with good outcomes — brains intact; ready to go. In real hospitals around that same time, only 15% of patients experienced such good outcomes. The vast majority of patients who experienced cardiac arrests in the hospital back then didn’t survive resuscitation efforts, and many of the ones who did survive, whose hearts were successfully restarted, still ended up either dying before leaving the hospital, or sustaining major brain damage.

That was then, though, and now hospital code teams have a new weapon in their resuscitory arsenal. That weapon is known as therapeutic hypothermia. In this procedure, medical professionals lower patients’ body temperatures dramatically at the time of resuscitation, and keep that temperature low for 12 to 48 hours, thereby reducing the need for oxygen in their brains. The result is significantly better outcomes. Two randomized clinical trials published in 2002 proved the benefits of therapeutic hypothermia. In one trial, 55% of patients receiving hypothermic treatment survived to hospital discharge with good neurologic outcomes — they could talk, they could read — versus only 39% who received standard treatment. In the other trial, these excellent outcomes were experienced by 49% of patients who received the temperature lowering treatment vs. only 26% who did not.

These are enormous benefits, by any measure. Consequently, the medical community was quick to embrace the benefits of therapeutic hypothermia. Indeed, the American Heart Association recommends therapeutic hypothermia as the standard of care for treatment of people experiencing cardiac arrests.

But some experts believe these guidelines have gone too far, and contend that energy and time put into therapeutic hypothermia, for the majority of hospitalized patients experiencing cardiac arrest, would be better spent elsewhere. “We know that therapeutic hypothermia works well in the kinds of patients enrolled in these two trials,” explains Dr. Kevin Riggs, an internist and ethicist at Johns Hopkins University, “but we do not know how well it works in the majority of hospitalized patients.”

Riggs explained to me that all the patients in those two groundbreaking trials experienced cardiac arrests due to either ventricular fibrillation or ventricular tachycardia, two electrical disturbances that are eminently treatable. If you are going to experience a cardiac arrest in a hospital (which I don’t recommend!), you want to have one of these two rhythms. A jolt of electricity could return your heart to its normal rhythm, something not so likely to happen with other causes of cardiac arrest.

“Look at the control groups from those two studies,” Riggs pointed out. “A quarter to almost 40% of them experienced great outcomes. That is not the norm in the hospital. Granted, the therapeutic hypothermia patients did even better, but the magnitude of the benefit probably resulted from just how treatable these patients were to begin with.”

Consider another group of patients — those whose hearts stop because of what doctors call “pulseless electrical activity.” In these patients, the electrocardiogram looks pretty good, like the heart ought to be beating normally, but the heart doesn’t beat. Patients resuscitated with this problem survive to hospital discharge less than 3% of the time. Now suppose those patients receive therapeutic hypothermia, and receive the same relative benefit as those patients did in the two research trials. In those studies, remember, survival rates were increased by a magnitude of about 1.5 — for example, from 39 to 55%. In the case of PEA, that would lead to an improvement in survival to discharge from 3% to less than 5%.

Now it is possible that the benefit of therapeutic hypothermia is larger than that. But estimating the benefits of therapeutic hypothermia in this kind of patient population is a matter of almost pure speculation, because to date — more than a decade after the two randomized trials were published — no one has conducted a randomized trial in patients with pulseless electrical activity. They have not conducted these studies in part because clinicians consider therapeutic hypothermia to be the standard of care, and therefore believe that randomizing people to a trial where half of them won’t receive it would be unethical. In fact, the physicians who wrote the editorial accompanying the two trials from 2002 called upon their colleagues to adopt “the use of mild hypothermia in survivors of cardiac arrest—as early as possible and for at least 12 hours.”

Two trials on a highly selective group of patients turned quickly into a treatment that all subsequent patients should receive?

If resources were infinite, such practice would be hard to dispute. Therapeutic hypothermia has no known side effects in survivors of cardiac arrest. But therapeutic hypothermia does have important costs. “It is very labor and time intensive,” explains Riggs, “diverting the efforts of intensive care and emergency department clinicians away from potentially more useful pursuits.”

Therapeutic hypothermia is expensive too, raising the cost of care over 30% according to one analysis.” If only 1 out of 100 PEA patients benefited from therapeutic hypothermia, such treatment would end up costing hundreds of thousands of dollars per patient benefited. “As a society, we should at least be debating this practice,” says Riggs. “We at least have to talk about whether this is the best way for us to spend health care dollars, at a time when we are desperate to control health care costs.”

In fact, what has happened to therapeutic hypothermia has happened to many health care interventions. An intervention is proven to benefit one group of patients, and is then offered to a wider and wider group of patients, many of whom are much less likely to benefit from the intervention. A cholesterol pill that is enormously beneficial to someone who just experienced a heart attack won’t be as helpful to someone unlikely to experience such a problem. A hip replacement that transforms the life of someone with severe arthritis won’t be as beneficial to someone with a milder disease. Nevertheless, we expand the population of patients for whom things like cholesterol pills and hip replacements are offered, and consequently the benefits of the interventions shrink while the harms remain relatively stable. We lose sight of the fact that sometimes the best medical intervention is not the most aggressive one.

Where does that leave us with new interventions to improve the care of people who experience cardiac arrest? Right now, I would say that Riggs is a lonely voice in the therapeutic hypothermia debate except for one fact: There is no debate. Therapeutic hypothermia has been accepted by health care professionals, adopted by professional societies, with no apparent reflection on which patients should and should not be receiving this treatment.

“I want to draw attention to the way medical intervention is diffused, from patient populations that benefit a lot from those interventions to those who have little to gain,” says Riggs. “I want to start a national conversation. I think therapeutic hypothermia is just the tip of an overtreatment iceberg.”

Time will tell whether Riggs succeeds in starting this conversation, and whether we, as a society, crash into Riggs’ metaphorical iceberg. Would it be trite to say that we are facing questions of Titanic proportions?